High Expression of Plasminogen Activator Inhibitor-2 (PAI-2) is a Predictor of Improved Survival in Patients with Pancreatic Adenocarcinoma

Excerpt

The characterization of molecular markers for prognostication in pancreatic cancer has become an important issue aiming to predict individual patient survival and the response to treatment.1 Several markers have shown their potential for that purpose including tumor oncogenes and suppressor genes, genes controlling apoptosis, tumor growth factors and their receptors and angiogenic factors.2 The interaction of tumour cells with the surrounding stroma is of particular importance for the invasion and metastasis of pancreatic cancer, and factors involved in the tumor – stroma interaction have shown significant prognostic potential. The urokinase plasminogen activator (uPA) and receptor (uPAR) which mediate cell invasion by matrix degradation and matrix metalloproteinase activation have been investigated in several solid tumors. In the present study, Smith and co-workers confirm previous data which demonstrate that high expression of uPA, uPAR and plasminogen activator inhibitor type 1 (PAI-1) are associated with a poor prognosis. The authors demonstrate that it is plasminogen activator inhibitor type 2 (PAI-2), which is the most significant factor of the uPA / PAI system that predicts survival independently in patients with pancreatic cancer both at a molecular and protein level (DOI: 10.1007/s00268-006-0289-9). The general impact of PAI-2 status needs to be confirmed by larger series, but the results of this study underline the importance of the uPA / PAI system as a predictive marker in pancreatic cancer. The strong correlation between PAI-2 mRNA and protein concentration would allow assessment of the PAI-2 status by immune-histochemistry rather than by complex molecular analysis. Apart from its significant association with survival and clinico-pathological characteristics, uPA / PAI may become a target for novel therapeutic strategies.3 However, it is important to consider that the various cascades of tumorgenesis and invasion are merely single pieces in the overall picture of carcinogenesis. Future work must determine the relationship and interplay between these cascades in more detail using micro-array and other techniques.4 …